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12/16/2011 @ 4:28PM11,863 views

With Death, Christopher Hitchens And Steve Jobs Showed Us The Limits Of DNA Sequencing

Christopher Hitchens, quite famously, did not believe in miracles. His death is a reminder that we shouldn’t, either – even when they’re the scientific kind.

Hitchens, like Steve Jobs, was among the first patients to benefit from a very new technology: the use of DNA sequencing to pick cancer drugs that might have a better chance of slowing a tumor’s growth.

Cells become cancerous because of mutations in their DNA that make them stop behaving as discrete parts of the body and instead cause them to multiply like crazy and run amok. Once a cell is cancer, its genes get twisted and re-arranged even more. The idea is that by identifying some of these mutations, doctors can figure out which drugs are most likely to stop or slow tumor growth and prolong life.

Jobs was so excited by this idea that he told his biographer, Walter Isaacson, that he could be among the first to outrun cancer this way or be among the last to die from it. Both DNA from Jobs’ tumor and Jobs’ own cells was sequenced — the most expensive and exhaustive way to look for tumor-causing defects. (A cheaper way is to just look at genes known to correlate with effectiveness for existing drugs in some cancers.)

Characteristically, Hitchens did not get nearly as excited as Jobs did about the prospect, but he still seemed filled with hope. “At least it spares me some of the boredom of being a cancer patient because what I’m going through is very absorbing and positively inspiring,” he told the Daily Telegraph. “But if it doesn’t work, I don’t know what they could try next.”

Also characteristically, the story of sequencing Hitchens’ tumor is full of larger-than-life debates about belief and nonbelief, God and the absence thereof. He was approached by Francis Collins, a devout Christian and head of the National Institutes of Health. A decade ago, Collins led the government-funded Human Genome Project, and he became deeply involved in Hitchens’ care.

In this video, aside from responding to the question, “Well Christopher, how are you feeling,” with “Well, I’m dying, but so are you,” Hitchens talks movingly about Collins, who he calls a great American, “one of the devout human beings I’ve ever met.”

Hitchens did find a drug that seemed to address one of his tumor’s mutations – it was reportedly Novartis’ Gleevec, the first targeted cancer drug – and that may have spared him some rounds of chemotherapy. But the medicine did not, of course, save him. Nor did it save Jobs.

According to Hitchens, Collins told him that he’s never seen anything in his medical career that could be called a miracle. That’s probably worth remembering as we begin to move into an era where many patients’ tumors will be sequenced. M.D. Anderson, where Hitchens died, has been trying to use DNA sequencing as a standard step in picking experimental drugs for patients; so have other cancer centers. One company, Foundation Medicine, which counts Google Ventures among its investors, is trying to turn this into a business model. Makers of DNA sequencing technology, including Illumina, Life Technologies, and Pacific Biosciences have been talking about the business opportunity for years.

This make sense because caring for late-stage cancer patients is so expensive, and so often futile, that even a costly technology like DNA sequencing (the price is dropping at an amazing rate but it’s still $5,000 or so for a full genome) could easily lead to improvements. But this technology is still in its early days, and it is not saving many lives just yet.

Update: Great point from
Evgeny Glazov on twitter: “Drug development is the real limit. Of all known genetic markers only a few are clinically actionable. Two in ~30 in acute myeloid leukemia.”

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It’s likely that 99% of the sequencing information was of little use to the care takers of these two patient. I’m not certain it takes a whole genome to know about glevex. Then again it also shows the main flaw of genome sequencing as a practical approach for clinical care. It just creates a huge data bust that not a lot of people can handle. The cost of sequencing is a simple and easy detail to fix in this equation, in fact it will not be part of the equation at all very soon. It will not really make any of this easier, yes it’s but no it’s not simple (Like going on Mars after the moon). Another issue that I find always amusing in these sories. A human might have a genome but a cancer is made up of many, many cells, sometimes cells we think are similar. These studies mostly sequence an average of cells, getting little or no information on the single or multi single cells involved in cancer. And that is a huge problem when looking for 0,05% somatic variation… It is still very much a needle in a haystack. (I won’t even go into the fact that cancer is not a steady state, it evolves and thus there is always a question of time course also, this is yet another dimension). Then of course we might have mundane data points to look at, such as the fact that maybe Mr Hitchens was still drinking his scotch versus a patient who would stop, that alone could engage in slight molecular changes. The complexity is endless and unfortunately Mr Collins is not the most objective person to evaluate the chances of genome sequencing against cancer therapy as opposed to a simple research tool for such mundane task as a super anti cancer vaccine.